chlorproguanil-dapsone-artesunate versus coartem for uncomplicated malaria

Conditions: Malaria, Falciparum

Summary: chlorproguanil-dapsone has been approved for the treatment of uncomplicated plasmodium falciparum malaria in a number of countries across sub-sahara africa, and by the uk's medicines and healthcare products regulatory agency. cda is a combination of chlorproguanil, dapsone and artesunate, being developed in a public-private partnership with the medicines for malaria venture (mmv), world health organisation (who-tdr) and academic partners from the london school of hygiene and tropical medicine, university of liverpool and the liverpool school of tropical medicine as a treatment for acute uncomplicated p. falciparum malaria. the combination of chlorproguanil-dapsone-artesunate (cda) is being developed to supersede chlorproguanil-dapsone for the same indication, but the addition of an artemisinin derivative, artesunate, should provide additional population benefits over chlorproguanil-dapsone alone. the artemisinins have been demonstrated to rapidly reduce parasite load and have activity against the sexual stages of the p.falciparum lifecycle. the addition of a second agent to the chlorproguanil-dapsone combination should also protect against the selection of resistant strains of p.falciparum. artemether-lumefantrine is the only available fixed-dose artemisinin-based combination therapy actually available and is considered as the gold standard for the treatment of p. falciparum malaria. this study will therefore aim to demonstrate the non-inferiority of the combination of cda to artemether-lumefantrine in terms of efficacy at 28-days. the key secondary objectives will compare the parasite clearance times (pct) and the fever clearance times (fct) between cda and artemether-lumefantrine.


Eligibility criteria:
inclusion criteria: * acute, uncomplicated p.falciparum malaria, microscopically confirmed * temperature at screening of 37.5oc or or more or confirmed history of fever within previous 24 hours * weigh 7.5kg or over * screening haemoglobin (hb) of 7g/dl or over, or haematocrit of 25% or more(if hb not available at screening) * willingness to comply with the study visits and procedures, as outlined in the informed consent form * written or oral witnessed consent has been obtained from parent or guardian * assent is given by a child aged 12 years or over, in addition to the consent of their parent or guardian exclusion criteria: * features of severe/complicated falciparum malaria * hypersensitivity to active substances (chlorproguanil, dapsone, artesunate, artemether, lumefantrine) * known allergy to biguanides, sulphones, sulphonamides, artemisinin derived products or aminoalcohol drugs * known history of g6pd deficiency * infants with a history of hyperbilirubinaemia during the neonatal period * use of concomitant medications that may induce haemolysis or haemolytic anaemia from the who (world health organization) list of essential drugs * evidence of any concomitant infection at the time of presentation (including p. vivax, p. ovale and p. malariae) * any other underlying disease that may compromise the diagnosis and the evaluation of the response to the study medication (including clinical symptoms of immunosuppression, tuberculosis, bacterial infection; cardiac or pulmonary disease) * malnutrition, defined as a child whose weight-for-height is below -3 standard deviations or less than 70% of the median of the nchs/who normalised reference values * treatment within the past three months with mefloquine or mefloquine-sulphadoxine-pyrimethamine; twenty-eight days with sulphadoxine/pyrimethamine, sulfalene/pyrimethamine, lumefantrine or artemether/lumefantrine, amodiaquine, atovaquone or atovoquone/proguanil, halofantrine; 14-days with chlorproguanil/dapsone, or 7-days with quinine (full course), proguanil, artemisinins, tetracycline doxycycline or clindamycin * positive sulphadoxine/pyrimethamine urine screen for 'unknown' antimalarial drug use in prior 28-days * use of an investigational drug within 30 days or 5 half-lives whichever is the longer * previous participation in this study * female subjects of child-bearing age, who have had a positive pregnancy test at screening, or do not give their consent to take a pregnancy test * female subjects who will be breast-feeding an infant for the duration of the study

Keywords: malaria cda coartem africa pediatrics children